Changes in the Serum Metabolome of Rats Following Intratracheal Instillation of Particles Representing Different Potential Mode-of-Action Categories of Nanomaterials

Details

• Personal Author:
  Antonini JM ; Boyce GR ; Fraser KE ; Hettick JM ; Kashon ML ; Kodali VK ; Powell MJ ; Roach KA ; Roberts, Jennifer R. ; Stefaniak, Aleksandr B.
• Description:
  With the expansion of nanotechnology, the number of workers potentially exposed to various emerging nanomaterials along their lifecycle increases creating the need to efficiently categorize different materials and their associated risks. Development of biomarkers of both particle exposure and the potential adverse outcomes is critical. Because of the rapid introduction of new materials to market, being able to categorize materials and the risks associated with them is also critical. The goal was to characterize the serum metabolome of different reference materials from different mode-of-action (MOA) categories [poorly soluble, low toxicity (nano-TiO2); poorly soluble, high toxicity (crystalline SiO2); higher solubility (nano-ZnO); and high aspect ratio (multi-walled carbon nanotubes-MWCNT)] for future development of biomarker panels that may be representative for different categories of nanomaterials. Male Sprague-Dawley rats were exposed by a single intratracheal-instillation to a low effect and high effect dose specific for each reference material or dispersion medium (DM; vehicle control): 0.100 or 1.00 mg nano-TiO2, 0.050 or 0.125 mg nano-ZnO, 0.050 or 0.250 mg SiO2, 0.010 or 0.500 mg MWCNT. Rats were euthanized at 2 days, 7 days, 1 month, and 3 months following an overnight fast. Lavage was performed on the right lungs to characterize lung injury and inflammation, and the left lung was preserved for pathology analysis. Serum was collected and prepared for relative quantitation of metabolites performed via high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), specifically using hydrophilic interaction liquid chromatography in the negative ion mode. Treatment groups were compared to DM animals to identify significantly altered metabolites. Lavage parameters showed that the high dose for each material caused significant lung injury and inflammation at 2 days which persisted throughout the time course for MWCNT and SiO2, with a trend for decreasing in MWCNT and increasing in SiO2. The low dose exposures, with the exception of nano-ZnO and MWCNT at 2 days and 7 days, did not cause significant toxicity. Parameters of toxicity were back to control levels for the high dose nano-ZnO at 1 month and the nano-TiO2 at 7 days post-exposure. Across all times and exposures, > 4000 compounds were identified in the serum samples, and these were associated with > 300 metabolic pathways. The most significant changes in metabolic profiles for all exposures were found at 7 days post exposure, with the number of downregulated molecules ranging from 12 - 47 and upregulated molecules ranging from 11-71, depending on the dose and the particle exposure. The number of significantly altered small molecules per group decreased dramatically with time. At the 3-month timepoint significantly increased and decreased molecules across the various exposures ranged from 0-21. Future studies will apply a bioinformatics approach to these significant alterations to develop small molecule biomarker panels that correspond to both the exposure and its associated adverse outcomes. [Description provided by NIOSH]
• Subjects:
  Animals Biomarkers Lung Occupational Exposure Occupational Health Respiratory System Safety Toxicology
• Keywords:
  Animal Studies Inhalation Studies Lung Tissue Nanomaterials Nanotoxicology Occupational Exposure
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; RHD - Respiratory Health Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  192
• NIOSHTIC Number:
  nn:20067232
• Citation:
  Toxicologist 2023 Mar; 192(S1):497
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7458e7ca9c71ae13d9ddd70003548a35b2dd5ee500dfde38d5b06c8abfe0f0af1658de23ba0cbca9910407a7cb8a54a11f0d3302091386463013a6f4ce44a28b
• Download URL:
  https://stacks.cdc.gov/view/cdc/231355/cdc_231355_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]